Interpretive Summary: Several parasite species cause malaria in human beings, but one is principally responsible for severe disease and death: Plasmodium falciparum. The evolutionary origins of this parasite are enigmatic, in spite of its dubious distinction as the leading infectious cause of human mortality. The idea that this parasite might have been acquired by human beings from birds was abandoned when it was realized that a closely related species of parasites occurs in our closest living relatives, the chimpanzees. Since then, many prominent studies have assumed that these malaria parasites co-speciated with their human and chimpanzee hosts, implying several million years of independent evolution. Here, we overturn this concept using new data (from parasites in chimpanzees) and demonstrate that P. falciparm diverged, only very recently, from ancestors harbored by chimpanzees. Like many other infections, the agent of human malaria had a zoonotic origin.

Technical Abstract:
Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known relative, the chimpanzee parasite, P. reichenowi, descended from distinct ancestors in their respective human and chimpanzee hosts 2. Here, we describe extensive diversity among several new isolates of P. reichenowi and demonstrate that their common ancestor also gave rise to P. falciparum. Evidently, the agent of malignant malaria was transferred once, to humans, from chimpanzees.